Fertilization: Difference between revisions

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[[File:Early_zygote_labelled.jpg|thumb|300px|Early Human Zygote]]
[[File:Early_zygote_labelled.jpg|thumb|300px|Early Human Zygote]]
[[Fertilization|Fertilization]] is the fusion of haploid gametes, egg and sperm, to form the diploid zygote. Note though there can be subtle differences in the {{fertilization}} process which occurs naturally within the body or through reproductive technologies outside the body, the overall product in both cases is a diplod zygote. In fertilization research, after humans the mouse is the most studied species followed by domestic and farm animals. The process of fertilization involves components of, and signaling between, both sperm ({{spermatozoa}}) and egg ({{oocyte}}).  
[[Fertilization|Fertilization]] is the fusion of haploid gametes, egg and sperm, to form the diploid zygote. Note though there can be subtle differences in the {{fertilization}} process which occurs naturally within the body or through reproductive technologies outside the body, the overall product in both cases is a diplod zygote. In fertilization research, after humans the mouse is the most studied species followed by domestic and farm animals. The process of fertilization involves components of, and signaling between, both sperm ({{spermatozoa}}) and egg ({{oocyte}}).  


In addition to ''in vivo'' fertilization there are many new '''in vitro''' technologies related to human infertility ([[Assisted Reproductive Technology]]) and animal production somatic cell nuclear transfer (SCNT) to generate a zygote.
In addition to ''in vivo'' fertilization there are many new '''in vitro''' technologies related to human infertility ([[Assisted Reproductive Technology]]) and animal production somatic cell nuclear transfer (SCNT) to generate a zygote.


Note different spelling - USA spelling "Fertilization", Australian spelling "Fertilisation".
Note different spelling - USA spelling "Fertilization", Australian spelling "Fertilisation".
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* '''Versatile action of picomolar gradients of progesterone on different sperm subpopulations'''{{#pmid:24614230}} "High step concentrations of progesterone may stimulate various sperm physiological processes, such as priming and the acrosome reaction. However, approaching the egg, spermatozoa face increasing concentrations of the hormone, as it is secreted by the cumulus cells and then passively diffuses along the cumulus matrix and beyond. ... The results suggest a versatile role of the gradual distribution of very low doses of progesterone, which selectively stimulate the priming and the acrosome reaction in different sperm subpopulations."
* '''Zinc sparks induce physiochemical changes in the egg zona pellucida that prevent polyspermy'''{{#pmid:28102396|PMID28102396}} "During fertilization or chemically-induced egg activation, the mouse egg releases billions of zinc atoms in brief bursts known as 'zinc sparks.' The zona pellucida (ZP), a glycoprotein matrix surrounding the egg, is the first structure zinc ions encounter as they diffuse away from the plasma membrane. Following fertilization, the ZP undergoes changes described as 'hardening', which prevent multiple sperm from fertilizing the egg and thereby establish a block to polyspermy. A major event in zona hardening is cleavage of ZP2 proteins by ovastacin; however, the overall physiochemical changes contributing to zona hardening are not well understood. These results provide a paradigm-shifting model in which fertilization-induced zinc sparks contribute to the polyspermy block by altering conformations of the ZP matrix. This adds a previously unrecognized factor, namely zinc, to the process of ZP hardening."
 
* '''Versatile action of picomolar gradients of progesterone on different sperm subpopulations'''{{#pmid:24614230|PMID24614230}} "High step concentrations of progesterone may stimulate various sperm physiological processes, such as priming and the acrosome reaction. However, approaching the egg, spermatozoa face increasing concentrations of the hormone, as it is secreted by the cumulus cells and then passively diffuses along the cumulus matrix and beyond. ... The results suggest a versatile role of the gradual distribution of very low doses of progesterone, which selectively stimulate the priming and the acrosome reaction in different sperm subpopulations."


* '''Juno is the egg Izumo receptor and is essential for mammalian fertilization'''{{#pmid:24739963|PMID24739963}} "Fertilization occurs when sperm and egg recognize each other and fuse to form a new, genetically distinct organism. The molecular basis of sperm–egg recognition is unknown, but is likely to require interactions between receptor proteins displayed on their surface. Izumo1 is an essential sperm cell-surface protein, but its receptor on the egg has not been described. Here we identify folate receptor 4 (Folr4) as the receptor for Izumo1 on the mouse egg, and propose to rename it Juno. We show that the Izumo1–Juno interaction is conserved within several mammalian species, including humans. Female mice lacking Juno are infertile and Juno-deficient eggs do not fuse with normal sperm. Rapid shedding of Juno from the oolemma after fertilization suggests a mechanism for the membrane block to polyspermy, ensuring eggs normally fuse with just a single sperm."
* '''Juno is the egg Izumo receptor and is essential for mammalian fertilization'''{{#pmid:24739963|PMID24739963}} "Fertilization occurs when sperm and egg recognize each other and fuse to form a new, genetically distinct organism. The molecular basis of sperm–egg recognition is unknown, but is likely to require interactions between receptor proteins displayed on their surface. Izumo1 is an essential sperm cell-surface protein, but its receptor on the egg has not been described. Here we identify folate receptor 4 (Folr4) as the receptor for Izumo1 on the mouse egg, and propose to rename it Juno. We show that the Izumo1–Juno interaction is conserved within several mammalian species, including humans. Female mice lacking Juno are infertile and Juno-deficient eggs do not fuse with normal sperm. Rapid shedding of Juno from the oolemma after fertilization suggests a mechanism for the membrane block to polyspermy, ensuring eggs normally fuse with just a single sperm."
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==Zona Pellucida==  
==Zona Pellucida==  
[[File:Mouse- zona pellucida 01.jpg|thumb|Mouse zona pellucida{{#pmid:18539589|PMID18539589}}]]
[[File:Mouse- zona pellucida 01.jpg|thumb|Mouse zona pellucida{{#pmid:18539589|PMID18539589}}]]
* glycoprotein shell ZP1, ZP2, ZP3, ZP4 (mouse only ZP1-3)
{{zona pellucida}} glycoprotein shell ZP1, ZP2, ZP3, ZP4 (mouse only ZP1-3)
* mechanical protection of egg  
 
* involved in the fertilization process  
# mechanical protection of egg  
* sperm binding  
# involved in the fertilization process  
* adhesion of sperm to egg  
# sperm binding  
* acrosome reaction  
# adhesion of sperm to egg  
** releases enzymes to locally breakdown  
# acrosome reaction  
* block of polyspermy  
# releases enzymes to locally breakdown  
** altered to prevent more than 1 sperm penetrating  
# cortical granules modify to block of polyspermy  
** may also have a role in development of the blastocyst
# altered to prevent more than 1 sperm penetrating  
# mechanical protection of zygote, blastomeres, morula and blastocyst
# role in development of the blastocyst




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* cells are also lost during transport along oviduct
* cells are also lost during transport along oviduct


==Gamete formation- Spermatogenesis==
==Spermatogenesis==
* process of spermatagonia mature into spermatazoa (sperm)  
* process of spermatagonia mature into spermatozoa (sperm)  
* continuously throughout life occurs in the seminiferous tubules in the male gonad- testis (plural testes)  
* continuously throughout life occurs in the seminiferous tubules in the male gonad- testis (plural testes)  
* at puberty spermatagonia activate and proliferate (mitosis)  
* at puberty spermatagonia activate and proliferate (mitosis)  
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:'''Links:''' [[Spermatozoa_Development|Spermatozoa Development]]
:'''Links:''' {{spermatozoa}}
==Ejaculate==
==Ejaculate==
* Human Ejaculate
* Human Ejaculate
** By volume <10 % sperm and accessory glands contribute majority of volume (60 % seminal vesicle, 10 % bulbourethral, 30 % prostate)
** By volume <10 % sperm and accessory glands contribute majority of volume (60 % seminal vesicle, 10 % bulbourethral, 30 % {{prostate}})
** 3.5 ml, 200-600 million sperm.
** 3.5 ml, 200-600 million sperm.
* Capacitation is the removal of glycoprotein coat and seminal proteins and alteration of sperm mitochondria.
* Capacitation is the removal of glycoprotein coat and seminal proteins and alteration of sperm mitochondria.
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:'''Links:''' [[Spermatozoa_Development|Spermatozoa]] | [[Prostate_Development|Prostate]]
:'''Links:''' {{spermatozoa}} | {{prostate}}
==Fertility Window==
==Fertility Window==
[[File:Menstrual cycle fertility probability 01.jpg|thumb|Probability of women with regular or irregular cycles being in their fertile window]]
[[File:Menstrual cycle fertility probability 01.jpg|thumb|Probability of women with regular or irregular cycles being in their fertile window]]
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* women should be advised that the timing of their fertile window can be highly unpredictable, even if their cycles are usually regular.
* women should be advised that the timing of their fertile window can be highly unpredictable, even if their cycles are usually regular.


:'''Links:''' {{menstrual cycle}}
==Fertilization Site==
==Fertilization Site==
[[File:Week1_summary.jpg|thumb|Week 1]]
[[File:Week1_summary.jpg|thumb|Week 1]]
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===Membrane Fusion===
===Membrane Fusion===
Spermatozoa and oocyte fusion in the membrane adhesion area requires the presence of 3 membrane proteins (spermatozoa Izumo1; oocyte receptor Juno and Cd9).{{#pmid:25209248|PMID25209248}}
Spermatozoa and oocyte fusion in the membrane adhesion area requires the presence of 3 membrane proteins (spermatozoa Izumo1; oocyte receptor Juno and Cd9).{{#pmid:25209248|PMID25209248}}
=== Izumo===
=== Izumo===


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'''Men - Y Chromosome'''
'''Men - Y Chromosome'''
* Y Chromosome carries Sry gene, protein product activates pathway for male gonad (covered in genital development)  
* {{ChrY}} Chromosome carries Sry gene, protein product activates pathway for male gonad (covered in genital development)  


'''Women - X Chromosome'''
'''Women - X Chromosome'''
* Gene dosage, one X chromosome in each female embryo cell has to be inactivated
* Gene dosage, one {ChrX}} chromosome in each female embryo cell has to be inactivated
* process is apparently random and  therefore 50% of cells have father's X, 50% have mother's X
* process is apparently random and  therefore 50% of cells have father's X, 50% have mother's X
* Note that because men only have 1 X chromosome, if abnormal, this leads to X-linked diseases more common in male that female where bothe X's need to be abnormal.
* Note that because men only have 1 X chromosome, if abnormal, this leads to X-linked diseases more common in male that female where bothe X's need to be abnormal.
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* The embryo (fetus, baby) does not develop at all but the placenta does grow.
* The embryo (fetus, baby) does not develop at all but the placenta does grow.


:'''Links:''' [[Abnormal Development - Hydatidiform Mole]]
:'''Links:''' {{hydatidiform mole}}


===Partial Hydatidiform Mole===
===Partial Hydatidiform Mole===
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* the three sets of chromosomes means the fetus is always grossly abnormal and will not survive.  
* the three sets of chromosomes means the fetus is always grossly abnormal and will not survive.  


:'''Links:''' [[Abnormal Development - Hydatidiform Mole]]
:'''Links:''' {{hydatidiform mole}}
===Parthenogenesis===
===Parthenogenesis===


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===Trisomy 21===
===Trisomy 21===
Trisomy 21 (Down's or Down syndrome) is caused by nondisjunction of chromosome 21 in a parent who is chromosomally normal and is one of the most common chromosomal aneuploidy abnormalities in liveborn children. The frequency of trisomy 21 in the population is approximately 1 in 650 to 1,000 live births, in Australia between 1991-97 there were 2,358 Trisomy 21 infants. There are other less frequently occurring trisomies (18, 13 and X).
{{Trisomy 21}} (Down's or Down syndrome) is caused by nondisjunction of chromosome 21 in a parent who is chromosomally normal and is one of the most common chromosomal aneuploidy abnormalities in liveborn children. The frequency of trisomy 21 in the population is approximately 1 in 650 to 1,000 live births, in Australia between 1991-97 there were 2,358 {{Trisomy 21}} infants. There are other less frequently occurring trisomies ({{Trisomy 18}}, {{Trisomy 13}} and {{Trisomy X}}).
 
 
:'''Links:''' {{Trisomy 21}}




:'''Links:''' [[Trisomy 21]]
==References==
==References==


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{{#pmid:29124919}}
{{#pmid:29124919}}
{{#pmid:27113677}}


{{#pmid:9557845}}
{{#pmid:9557845}}

Revision as of 14:21, 15 May 2018

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Introduction

Human fertilization
Human Fertilization
Early Human Zygote

Fertilization is the fusion of haploid gametes, egg and sperm, to form the diploid zygote. Note though there can be subtle differences in the fertilization process which occurs naturally within the body or through reproductive technologies outside the body, the overall product in both cases is a diplod zygote. In fertilization research, after humans the mouse is the most studied species followed by domestic and farm animals. The process of fertilization involves components of, and signaling between, both sperm (spermatozoa) and egg (oocyte).


In addition to in vivo fertilization there are many new in vitro technologies related to human infertility (Assisted Reproductive Technology) and animal production somatic cell nuclear transfer (SCNT) to generate a zygote.


Note different spelling - USA spelling "Fertilization", Australian spelling "Fertilisation".

The first polar body deforms the mammalian egg away from its encapsulating zona pellucida


Fertilization Links: fertilization | oocyte | spermatozoa | meiosis | | ovary | testis | menstrual cycle | zona pellucida | zygote | granulosa cell Lecture - Fertilization | 2016 Lecture | mitosis | Lecture - Week 1 and 2 | hydatidiform mole | Assisted Reproductive Technology | | morula | blastocyst | Lecture - Genital Development | Category:Fertilization
Historic Embryology - Fertilization 
1910 Fertilization | 1919 Human Ovum | 1921 The Ovum | 1927 First polar body | 1929 Oocyte Size | 1943 Fertilization | 1944 In vitro fertilization | 1948 In vitro fertilization



Human-spermatozoa EM01.jpg

Some Recent Findings

  • Zinc sparks induce physiochemical changes in the egg zona pellucida that prevent polyspermy[1] "During fertilization or chemically-induced egg activation, the mouse egg releases billions of zinc atoms in brief bursts known as 'zinc sparks.' The zona pellucida (ZP), a glycoprotein matrix surrounding the egg, is the first structure zinc ions encounter as they diffuse away from the plasma membrane. Following fertilization, the ZP undergoes changes described as 'hardening', which prevent multiple sperm from fertilizing the egg and thereby establish a block to polyspermy. A major event in zona hardening is cleavage of ZP2 proteins by ovastacin; however, the overall physiochemical changes contributing to zona hardening are not well understood. These results provide a paradigm-shifting model in which fertilization-induced zinc sparks contribute to the polyspermy block by altering conformations of the ZP matrix. This adds a previously unrecognized factor, namely zinc, to the process of ZP hardening."
  • Versatile action of picomolar gradients of progesterone on different sperm subpopulations[2] "High step concentrations of progesterone may stimulate various sperm physiological processes, such as priming and the acrosome reaction. However, approaching the egg, spermatozoa face increasing concentrations of the hormone, as it is secreted by the cumulus cells and then passively diffuses along the cumulus matrix and beyond. ... The results suggest a versatile role of the gradual distribution of very low doses of progesterone, which selectively stimulate the priming and the acrosome reaction in different sperm subpopulations."
  • Juno is the egg Izumo receptor and is essential for mammalian fertilization[3] "Fertilization occurs when sperm and egg recognize each other and fuse to form a new, genetically distinct organism. The molecular basis of sperm–egg recognition is unknown, but is likely to require interactions between receptor proteins displayed on their surface. Izumo1 is an essential sperm cell-surface protein, but its receptor on the egg has not been described. Here we identify folate receptor 4 (Folr4) as the receptor for Izumo1 on the mouse egg, and propose to rename it Juno. We show that the Izumo1–Juno interaction is conserved within several mammalian species, including humans. Female mice lacking Juno are infertile and Juno-deficient eggs do not fuse with normal sperm. Rapid shedding of Juno from the oolemma after fertilization suggests a mechanism for the membrane block to polyspermy, ensuring eggs normally fuse with just a single sperm."
More recent papers  
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Search term: Fertilization

<pubmed limit=5>Fertilization</pubmed>

Older papers  
  • Non-genetic contributions of the sperm nucleus to embryonic development[4] "Recent data from several laboratories have provided evidence that the newly fertilized oocyte inherits epigenetic signals from the sperm chromatin that are required for proper embryonic development. For the purposes of this review, the term epigenetic is used to describe all types of molecular information that are transmitted from the sperm cell to the embryo. There are at least six different forms of epigenetic information that have already been established as being required for proper embryogenesis in mammals or for which there is evidence that it may do so. These are (i) DNA methylation; (ii) sperm-specific histones, (iii) other chromatin-associated proteins; (iv) the perinuclear theca proteins; (v) sperm-born RNAs and, the focus of this review; and (vi) the DNA loop domain organization by the sperm nuclear matrix. These epigenetic signals should be considered when designing protocols for the manipulation and cryopreservation of spermatozoa for assisted reproductive technology as necessary components for effective fertilization and subsequent embryo development."
  • CD9 tetraspanin generates fusion competent sites on the egg membrane for mammalian fertilization[5] "CD9 tetraspanin is the only egg membrane protein known to be essential for fertilization. To investigate its role, we have measured, on a unique acrosome reacted sperm brought in contact with an egg, the adhesion probability and strength with a sensitivity of a single molecule attachment. Probing the binding events at different locations of wild-type egg we described different modes of interaction. Here, we show that more gamete adhesion events occur on Cd9 null eggs but that the strongest interaction mode disappears. We propose that sperm-egg fusion is a direct consequence of CD9 controlled sperm-egg adhesion properties. CD9 generates adhesion sites responsible for the strongest of the observed gamete interaction. These strong adhesion sites impose, during the whole interaction lifetime, a tight proximity of the gamete membranes, which is a requirement for fusion to take place. The CD9-induced adhesion sites would be the actual location where fusion occurs."
  • Gamete recognition in mice depends on the cleavage status of an egg's zona pellucida protein[6] "sperm-egg recognition depends on the cleavage status of ZP2 and that binding at the surface of the zona is not sufficient to induce sperm acrosome exocytosis."

Objectives

  • Understand the mechanisms of gamete formation.
  • Understand the mechanisms of cell division.
  • Describe the differences between mitosis and meiosis.
  • Understand the mechanisms of fertilization, both in vivo and in vitro.
  • Describe the cleavage of the zygote.
  • Have a preliminary understanding of the role and process in male sex determination and X inactivation.
  • Understand the abnormalities that occur during this period of development.

Movies

Follicle 001 icon.jpg
 ‎‎Ovulation
Page | Play
Spermatozoa animation icon.jpg
 ‎‎Spermatozoa
Page | Play
Spermatozoa motility icon 01.jpg
 ‎‎Spermatozoa Motility
Page | Play
Human fertilization 1 icon.jpg
 ‎‎Fertilisation to
4 Blastomere
Page | Play
Human fertilization 2 icon.jpg
 ‎‎Fertilization
Page | Play
Fertilization 002 icon.jpg
 ‎‎Fertilization
Page | Play
Fertilization 001 icon.jpg
 ‎‎Mouse Fertilisation
Page | Play
Pronuclear fusion 001 icon.jpg
 ‎‎Pronuclear Fusion
Page | Play
Week1 001 icon.jpg
 ‎‎Week 1
Page | Play

Fertilization Preparation

Prior to the fertilization process commencing both the gametes oocyte (egg) and spermatozoa (sperm) require completion of a number of biological processes.

  • Oocyte meiosis - completes Meiosis 1 and commences Meiosis 2 (arrests at Metaphase II).
  • Spermatozoa Capacitation - following release (ejaculation) and mixing with other glandular secretions, activates motility and acrosome preparation.
  • Migration - both oocyte and spermatozoa.
    • oocyte ovulation and release with associated cells, from ovary into fimbria then into uterine tube (oviduct, uterine horn, fallopian tube) and epithelial cilia mediated movement.
    • spermatozoa ejaculation, deposited in vagina, movement of tail to "swim" in uterine secretions through cervix, uterine body and into uterine tube, have approximately 24-72h to fertilize oocyte.

Endocrinology - Diagram of the comparative anatomy of the male and female reproductive tracts

Oogenesis

Histology of the Ovary
Preantral Follicle
Antral Follicle and Oocyte
  • Process of oogonia mature into oocytes (ova, ovum, egg)
  • all oogonia form primary oocytes before birth, therefore a maturation of preexisting cells in the female gonad, ovary

Human ovary non-growing follicle model.jpg

  • humans usually only 1 ovum released every menstrual cycle (IVF- superovulation)
  • oocyte and its surrounding cells = follicle
  • primary -> secondary -> ovulation releases

Ovary- Histology - whole transverse section (cortex, medulla)

Menstrual Cycle

  • Primary Oocyte - arrested at early Meiosis 1
    • diploid: 22 chromosome pairs + 1 pair X chromosomes (46, XX)
    • autosomes and sex chromosome
  • Oogenesis- pre-antral then antral follicle (Graafian follicle is mature antral follicle released)
  • Secondary oocyte
    • 1 Day before ovulation completes (stim by LH) Meiosis 1
    • haploid: 22 chromosomes + 1 X chromosome (23, X)
    • nondisjunction- abnormal chromosome segregation
    • begins Meiosis 2 and arrests at metaphase
    • note no interphase replication of DNA, only fertilization will complete Meiosis 2

Ovulation (HPG Axis)

Menstrual cycle.png

  • Hypothalmus releases gonadotropin releasing hormone (GRH, luteinizing hormone–releasing hormone, LHRH) -> Pituitary releases follicle stimulating hormone (FSH) and lutenizing hormone (LH) -> ovary follicle development and ovulation.
    • release of the secondary oocyte and formation of corpus luteum
    • secondary oocyte encased in zona pellucida and corona radiata
  • Ovulation associated with follicle rupture and ampulla movement.

Zona Pellucida

Mouse zona pellucida[7]

zona pellucida glycoprotein shell ZP1, ZP2, ZP3, ZP4 (mouse only ZP1-3)

  1. mechanical protection of egg
  2. involved in the fertilization process
  3. sperm binding
  4. adhesion of sperm to egg
  5. acrosome reaction
  6. releases enzymes to locally breakdown
  7. cortical granules modify to block of polyspermy
  8. altered to prevent more than 1 sperm penetrating
  9. mechanical protection of zygote, blastomeres, morula and blastocyst
  10. role in development of the blastocyst


Links: zona pellucida | MBoC - Figure 20-21. The zona pellucida

Corona Radiata

Mouse granulosa cells
Mouse granulosa cells[8]
  • granulosa cells and extracellular matrix
  • protective and nutritional role for cells during transport
  • cells are also lost during transport along oviduct

Spermatogenesis

  • process of spermatagonia mature into spermatozoa (sperm)
  • continuously throughout life occurs in the seminiferous tubules in the male gonad- testis (plural testes)
  • at puberty spermatagonia activate and proliferate (mitosis)
  • primary spermatocyte -> secondary spermatocyte-> spermatid->sperm
  • Seminiferous Tubule is site of maturation involving meiosis and spermiogenesis
  • Spermatogenesis- Meiosis
  • meiosis is reductive cell division
    • 1 spermatagonia (diploid) 46, XY (also written 44+XY) = 4 sperm (haploid); 23, X 23, X 23, Y 23, Y

Spermiogenesis

  • morphological (shape) change from round spermatids to elongated sperm
  • loose cytoplasm
  • Transform golgi apparatus into acrosome (in head)
  • Organize microtubules for motility (in tail, flagellum)
  • Segregate mitochondria for energy (in tail)


Links: spermatozoa

Ejaculate

  • Human Ejaculate
    • By volume <10 % sperm and accessory glands contribute majority of volume (60 % seminal vesicle, 10 % bulbourethral, 30 % prostate)
    • 3.5 ml, 200-600 million sperm.
  • Capacitation is the removal of glycoprotein coat and seminal proteins and alteration of sperm mitochondria.
  • Ovulation-inducing factor identified in several species.[9]
  • Infertility can be due to Oligospermia, Azoospermia, Immotile Cilia Syndrome
    • Oligospermia (Low Sperm Count) - less than 20 million sperm after 72 hour abstinence from sex
    • Azoospermia (Absent Sperm) - blockage of duct network
    • Immotile Cilia Syndrome - lack of sperm motility


Links: spermatozoa | prostate

Fertility Window

Probability of women with regular or irregular cycles being in their fertile window

Clinical guidelines have typically identified the "fertile window" between days 10 and 17 within the typical 28 day menstrual cycle.

Data from a large USA NIEHS - Early Pregnancy Study (1982-86) identified the timing of the “fertile window” within a range of different menstrual cycles.[10]

  • fertile window occurred during a broad range of days in the menstrual cycle.
  • between days 6 and 21 women had at minimum a 10% probability of being in their fertile window.
  • women cannot predict a sporadic late ovulation; 4 - 6% of women whose cycles had not yet resumed were potentially fertile in the fifth week of their cycle.
  • only about 30% of women is the fertile window entirely within the days of the menstrual cycle identified by clinical guidelines (between days 10 and 17)
  • most women reach their fertile window earlier and others much later.
  • women should be advised that the timing of their fertile window can be highly unpredictable, even if their cycles are usually regular.
Links: menstrual cycle

Fertilization Site

Week 1
  • Fertilization usually occurs in first 1/3 of oviduct
  • Fertilization can also occur outside oviduct, associated with In Vitro Fertilization (IVF, GIFT, ZIFT...) and ectopic pregnancy
  • The majority of fertilized eggs do not go on to form an embryo

Fertilization - Spermatozoa

  • Contact between spermatozoa and oocyte egg coat (zona pellucida [ZP]) glycoproteins triggers increases in intracellular calcium ion (iCa2+) concentration in spermatozoa[11]
  • CATSPER channels on the distal portion of sperm (the principal piece) are required for the ZP-induced iCa2+ increases
  • iCa2+ increase starts from the spermatozoa tail and propagates toward the head
  • Store depletion-activated Ca2+ entry is thought to mediate the sustained phase

Fertilization - Oocyte

Spermatozoa - Oocyte Interaction

Membrane Fusion

Spermatozoa and oocyte fusion in the membrane adhesion area requires the presence of 3 membrane proteins (spermatozoa Izumo1; oocyte receptor Juno and Cd9).[12]

Izumo

The sperm-specific protein Izumo is named for a Japanese shrine dedicated to marriage and is essential for sperm-egg plasma membrane binding and fusion. It interacts with the spermatozoa folate receptor 4 (Folr4).

Links: OMIM 609278

Juno

folate receptor 4 (Folr4)

Folate receptors are also known as the folic acid (FA) binding protein and bind of 5-methyltetrahydrofolate (5-MeTHF).

CD9

Oocyte cell surface protein acts as a receptor for pregnancy-specific glycoprotein 17 (Psg17).


Links: OMIM 143030

Ovastacin

(Astacin-Like Metalloendopeptidase, ASTL) An oocyte enzyme (zinc-dependent metalloprotease) involved in altering zona pellucida structure, by cleaving zona pellucida glycoprotein (ZP2), following fertilisation.[13] This change in zona pellucida structure is one of the blockers to polyspermy.
Mouse oocyte cortical granule (green) ovastacin (red) staining.[13]

Formation of the Zygote

Early human zygote showing Pronuclei
  • Pronuclei - Male and Female haploid nuclei approach each other and nuclear membranes break down
  • chromosomal pairing, DNA replicates, first mitotic division
  • Spermatozoa contributes - centriole which organizes mitotic spindle
  • Oocyte contributes - mitochondria (maternally inherited)


Mitochondria

  • Mitochondria of the spermatozoa are specifically destroyed in early development by proteolysis (mouse 4 to 8 cell transition).[14]
  • Metaphase II oocytes in rats have an average mitochondrial DNA (mtDNA) copy number of 147,600 (+/-3000) that only increases at the 8-cell stage.[15]

Sex Determination

  • based upon whether an X or Y carrying sperm has fertilized the egg, should be 1.0 sex ratio.
  • actually 1.05, 105 males for every 100 females, some studies show more males 2+ days after ovulation.
  • cell totipotent (equivalent to a stem cell, can form any tissue of the body)

Men - Y Chromosome

  • Y Chromosome carries Sry gene, protein product activates pathway for male gonad (covered in genital development)

Women - X Chromosome

  • Gene dosage, one {ChrX}} chromosome in each female embryo cell has to be inactivated
  • process is apparently random and therefore 50% of cells have father's X, 50% have mother's X
  • Note that because men only have 1 X chromosome, if abnormal, this leads to X-linked diseases more common in male that female where bothe X's need to be abnormal.

Fertilization Protein Changes

A recent study in mice has shown that after fertilization the maternal proteins present in the original oocyte are quickly degraded by the zygote stage. MII oocytes have 185,643 different peptides while zygotes contain only 85,369 peptides.[16]

Protein Expression Classified by Molecular Functions

MII oocyte
Zygote
Mouse- MII oocyte protein expression.jpg Mouse- zygote protein expression.jpg

Abnormalities

Trisomy 21

The abnormalities listed below relate to genetic abnormalities occurring during fertilisation. There are of course many additional genetic abnormalities inherited and introduced by the recombined maternal and paternal genomes, other than trisomy 21 these will not be covered here.

Complete Hydatidiform Mole

  • Chromosomal genetic material from the oocyte (ovum, egg) is lost, by an unknown process.
  • Fertilization then occurs with one or two spermatozoa and an androgenic (from the male only) conceptus (fertilized oocyte) is formed.
  • The embryo (fetus, baby) does not develop at all but the placenta does grow.
Links: hydatidiform mole

Partial Hydatidiform Mole

Three sets of chromosomes instead of the usual two and this is called triploidy.

  • chromosomal (genetic) material from the oocyte (ovum, egg) is retained and the egg is fertilized by one or two spermatozoa.
  • with partial mole there are maternal chromosomes and there is a fetus.
  • the three sets of chromosomes means the fetus is always grossly abnormal and will not survive.
Links: hydatidiform mole

Parthenogenesis

(Greek, parthenos = virgin, genesis = birth) The development of an unfertilized oocyte (no spermatozoa). Other than mammals, many different species (plants, insects, reptiles) can develop from unfertilized eggs. An embryo so formed without sperm contribution. Blocking of parthenogenesis in mammals appears to be related to genomic imprinting. Abnormal parthenogenic processes can occur in mammals, and more recently a parthenogenic mouse has been made in the laboratory.


Trisomy 21

Trisomy 21 (Down's or Down syndrome) is caused by nondisjunction of chromosome 21 in a parent who is chromosomally normal and is one of the most common chromosomal aneuploidy abnormalities in liveborn children. The frequency of trisomy 21 in the population is approximately 1 in 650 to 1,000 live births, in Australia between 1991-97 there were 2,358 Trisomy 21 infants. There are other less frequently occurring trisomies (Trisomy 18, Trisomy 13 and Trisomy X).


Links: Trisomy 21


References

  1. Que EL, Duncan FE, Bayer AR, Philips SJ, Roth EW, Bleher R, Gleber SC, Vogt S, Woodruff TK & O'Halloran TV. (2017). Zinc sparks induce physiochemical changes in the egg zona pellucida that prevent polyspermy. Integr Biol (Camb) , 9, 135-144. PMID: 28102396 DOI.
  2. Uñates DR, Guidobaldi HA, Gatica LV, Cubilla MA, Teves ME, Moreno A & Giojalas LC. (2014). Versatile action of picomolar gradients of progesterone on different sperm subpopulations. PLoS ONE , 9, e91181. PMID: 24614230 DOI.
  3. Bianchi E, Doe B, Goulding D & Wright GJ. (2014). Juno is the egg Izumo receptor and is essential for mammalian fertilization. Nature , 508, 483-7. PMID: 24739963 DOI.
  4. Yamauchi Y, Shaman JA & Ward WS. (2011). Non-genetic contributions of the sperm nucleus to embryonic development. Asian J. Androl. , 13, 31-5. PMID: 20953203 DOI.
  5. Jégou A, Ziyyat A, Barraud-Lange V, Perez E, Wolf JP, Pincet F & Gourier C. (2011). CD9 tetraspanin generates fusion competent sites on the egg membrane for mammalian fertilization. Proc. Natl. Acad. Sci. U.S.A. , 108, 10946-51. PMID: 21690351 DOI.
  6. Gahlay G, Gauthier L, Baibakov B, Epifano O & Dean J. (2010). Gamete recognition in mice depends on the cleavage status of an egg's zona pellucida protein. Science , 329, 216-9. PMID: 20616279 DOI.
  7. Wassarman PM. (2008). Zona pellucida glycoproteins. J. Biol. Chem. , 283, 24285-9. PMID: 18539589 DOI.
  8. Zhou HX, Ma YZ, Liu YL, Chen Y, Zhou CJ, Wu SN, Shen JP & Liang CG. (2014). Assessment of mouse germinal vesicle stage oocyte quality by evaluating the cumulus layer, zona pellucida, and perivitelline space. PLoS ONE , 9, e105812. PMID: 25144310 DOI.
  9. Ratto MH, Leduc YA, Valderrama XP, van Straaten KE, Delbaere LT, Pierson RA & Adams GP. (2012). The nerve of ovulation-inducing factor in semen. Proc. Natl. Acad. Sci. U.S.A. , 109, 15042-7. PMID: 22908303 DOI.
  10. Wilcox AJ, Dunson D & Baird DD. (2000). The timing of the "fertile window" in the menstrual cycle: day specific estimates from a prospective study. BMJ , 321, 1259-62. PMID: 11082086
  11. Xia J & Ren D. (2009). Egg coat proteins activate calcium entry into mouse sperm via CATSPER channels. Biol. Reprod. , 80, 1092-8. PMID: 19211808 DOI.
  12. Chalbi M, Barraud-Lange V, Ravaux B, Howan K, Rodriguez N, Soule P, Ndzoudi A, Boucheix C, Rubinstein E, Wolf JP, Ziyyat A, Perez E, Pincet F & Gourier C. (2014). Binding of sperm protein Izumo1 and its egg receptor Juno drives Cd9 accumulation in the intercellular contact area prior to fusion during mammalian fertilization. Development , 141, 3732-9. PMID: 25209248 DOI.
  13. 13.0 13.1 Burkart AD, Xiong B, Baibakov B, Jiménez-Movilla M & Dean J. (2012). Ovastacin, a cortical granule protease, cleaves ZP2 in the zona pellucida to prevent polyspermy. J. Cell Biol. , 197, 37-44. PMID: 22472438 DOI.
  14. Cummins JM. (2000). Fertilization and elimination of the paternal mitochondrial genome. Hum. Reprod. , 15 Suppl 2, 92-101. PMID: 11041517
  15. Kameyama Y, Filion F, Yoo JG & Smith LC. (2007). Characterization of mitochondrial replication and transcription control during rat early development in vivo and in vitro. Reproduction , 133, 423-32. PMID: 17307910 DOI.
  16. Wang S, Kou Z, Jing Z, Zhang Y, Guo X, Dong M, Wilmut I & Gao S. (2010). Proteome of mouse oocytes at different developmental stages. Proc. Natl. Acad. Sci. U.S.A. , 107, 17639-44. PMID: 20876089 DOI.

Textbooks

  • Human Embryology (2nd ed.) Larson Ch1 p1-32
  • The Developing Human: Clinically Oriented Embryology (6th ed.) Moore and Persaud
  • Before we Are Born (5th ed.) Moore and Persaud Ch 2 p14-33
  • Essentials of Human Embryology Larson Ch1 p1-16
  • Human Embryology Fitzgerald and Fitzgerald Ch2 p8-14

Search NCBI Bookshelf fertilization | fertilisation

Reviews

Bianchi E & Wright GJ. (2016). Sperm Meets Egg: The Genetics of Mammalian Fertilization. Annu. Rev. Genet. , 50, 93-111. PMID: 27617973 DOI.

Mou L & Xie N. (2017). Male infertility-related molecules involved in sperm-oocyte fusion. J. Reprod. Dev. , 63, 1-7. PMID: 27904014 DOI.

Articles

Suzuki B, Sugano Y, Ito J, Saito H, Niimura S & Yamashiro H. (2017). Location and expression of Juno in mice oocytes during maturation. JBRA Assist Reprod , 21, 321-326. PMID: 29124919 DOI.

Duncan FE, Que EL, Zhang N, Feinberg EC, O'Halloran TV & Woodruff TK. (2016). The zinc spark is an inorganic signature of human egg activation. Sci Rep , 6, 24737. PMID: 27113677 DOI.

Wilcox AJ, Weinberg CR & Baird DD. (1998). Post-ovulatory ageing of the human oocyte and embryo failure. Hum. Reprod. , 13, 394-7. PMID: 9557845

Search Pubmed

April 2010

  • fertilization - All (51803) Review (5928) Free Full Text (11715)


Search Pubmed Now: fertilization | fertilisation | zona pellucida | zygote

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Cite this page: Hill, M.A. (2024, March 29) Embryology Fertilization. Retrieved from https://embryology.med.unsw.edu.au/embryology/index.php/Fertilization

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